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Cited by 529Protein Kinase Regulation and GTPase SignalingPI3K/AKT/mTOR signaling in cancerSphingolipid Metabolism and Signaling

Mammalian Phospholipase C

Kadamur, Ganesh, Ross, Elliott M.·2013·Annual Review of Physiology
DOI 10.1146/annurev-physiol-030212-183750
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Abstract

Phospholipase C (PLC) converts phosphatidylinositol 4,5-bisphosphate (PIP(2)) to inositol 1,4,5-trisphosphate (IP(3)) and diacylglycerol (DAG). DAG and IP(3) each control diverse cellular processes and are also substrates for synthesis of other important signaling molecules. PLC is thus central to many important interlocking regulatory networks. Mammals express six families of PLCs, each with both unique and overlapping controls over expression and subcellular distribution. Each PLC also responds acutely to its own spectrum of activators that includes heterotrimeric G protein subunits, protein tyrosine kinases, small G proteins, Ca(2+), and phospholipids. Mammalian PLCs are autoinhibited by a region in the catalytic TIM barrel domain that is the target of much of their acute regulation. In combination, the PLCs act as a signaling nexus that integrates numerous signaling inputs, critically governs PIP(2) levels, and regulates production of important second messengers to determine cell behavior over the millisecond to hour timescale.

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Crossref · 10.1146/annurev-physiol-030212-183750

Cites

193 of 193 references verified0 citation errors · 0 not checkable

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  • PLCγ2 activity can induce calcium influx from the ER through the binding of IP3 to its receptor IP3R.

    “PLCγ2 activity can induce calcium influx from the ER through the binding of IP3 to its receptor in the ER, IP3R [26].”

    From Heterozygous expression of the Alzheimer’s disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses (2022) · cites this paper as [26]

  • This massive cytoplasmic Ca2+ influx is critical for various downstream signalling pathways that modulate numerous microglial functions.

    “This massive cytoplasmic Ca2+ influx is critical for various downstream signalling pathways that modulate numerous microglial functions.”

    From Heterozygous expression of the Alzheimer’s disease-protective PLCγ2 P522R variant enhances Aβ clearance while preserving synapses (2022) · cites this paper as [26]

  • Mammalian PLC enzymes that use phosphoinositides, preferentially PI(4,5)P2, are grouped into six families (β, γ, δ, ε, ζ and η).

    “In mammals, PLC enzymes that use phosphoinositides (preferentially PI(4,5)P2) as their substrates have been grouped into six families (β, γ, δ, ε, ζ and η).”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [27]

  • There are thirteen PLCs in mammals: four PLCβ, two PLCγ, three PLCδ, one PLCε, one PLCζ and two PLCη.

    “Within each family are multiple members: four PLCβ (1–4), two PLCγ (1 and 2), three PLCδ (1, 3, 4), one PLCε, one PLCζ and two PLCη (1 and 2) making thirteen PLCs in total (reviewed in [27–33]) (Figure 3A).”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [27]

  • Signalling connectivity is best defined for GPCRs and PLCβ isoforms via G-protein α and βγ subunits, and for RTKs and tyrosine kinases linked to ITAM-associated receptors that activate PLC enzymes by direct phosphorylation.

    “Overall, the signalling connectivity remains best defined for the G-protein coupled receptors (GPCRs) and PLCβ isoforms, mediated by the α and βγ subunits of G-proteins, and for the RTKs and tyrosine kinases linked to immunoreceptor tyrosine-based activation motif (ITAM)-associated receptors, that activate PLC enzymes by direct phosphorylation.”

    From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [27]

Cites

Flagged first, then by citations

Research works printed but not linked: 5

  1. Powis G, 1992, Cancer Res., 52, 2835
  2. Beekman A, 1998, Cancer Res., 58, 910
  3. Ross EM, 1994, Endothelium-Derived Factors and Vascular Functions, 211
  4. Ross EM, 1995, Rec. Prog. Horm. Res., 50, 207
  5. Stewart AJ, 2005, Int. J. Mol. Med., 15, 117

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Authors
Kadamur, G., & Ross, E. M.
Affiliations
The University of Texas Southwestern Medical Center (US)
ORCID
Venue
Annual Review of Physiology
Publisher
Annual Reviews
Published
2013-02-10
Volume
75
Issue
1
Pages
127-154
ISSN
  • 0066-4278 (ISSN-L)
  • 1545-1585
DOI
10.1146/annurev-physiol-030212-183750
OpenAlex
W2117913181
Cited by
529
References
193
Citations by year
2026: 24 · 2025: 38 · 2024: 47 · 2023: 46 · 2022: 45 · 2021: 50 · 2020: 50 · 2019: 49 · 2018: 43 · 2017: 35 · 2016: 25 · 2015: 27 · 2014: 32 · 2013: 14 · 2012: 3
FWCI
1.57
Type
journal article
Language
en
Open access
closed
Locations
  • Annual Review of Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • University of Texas Southwestern Medical Center
  • National Institutes of Health
  • U.S. Public Health Service (R01MG030355)
  • National Institute of General Medical Sciences (R01GM030355)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
Keywords
phospholipase C, phosphatidylinositol 4,5-bisphosphate, inositol 1,4,5-trisphosphate, diacylglycerol, second messengers, G protein signaling, tyrosine kinase, small GTPases, calcium regulation, autoinhibition, signal integration, subcellular localization
MeSH terms
Animals, Diglycerides, Humans, Type C Phospholipases, Second Messenger Systems, Signal Transduction, Inositol 1,4,5-Trisphosphate, Phosphatidylinositol 4,5-Diphosphate

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